Process for preparing carotenoid polyene chain compounds and intermediates for preparing the same

ABSTRACT

The present invention provides an intermediate compound used for synthesis of polyene chain structure, that is an important moiety of carotenoid compounds, a process for preparing the same, and carotenoid polyene chain compounds prepared by using the intermediate, and, in particular, a process for preparing lycopene. The process for preparing the carotenoid polyene chain compound employs an allylic sulfone compound as starting material, which is reacted with C-5 sulfide compound to extend the carbon chain. The resultant thio-sulfone compound is oxidized, and the obtained disulfone compound is combined with C-10 di(haloallylic) sulfide compound to form a chain compound containing the desired number of carbon atoms. Then, the diallylic sulfone obtained by oxidation of the diallylic sulfide is subjected to Ramberg-Baklund reaction in order to form the central triene bond. After removal of sulfonyl groups, carotenoid polyene chain compound is obtained.

TECHNICAL FIELD

The present invention relates to a process for preparing carotenoidpolyene chain compounds. More specifically, it relates to intermediatecompounds which are useful for synthesis of carotenoid compounds havingpolyene chain structure, and a process for preparing the same, and aprocess for preparing polyene chain compounds, especially lycopene, byusing the intermediate compound.

BACKGROUND ART

Carotenoid compounds have polyene chain structure. Specific examples ofthe compounds include beta-carotene, lycopene, astaxanthin, bixin, andthe like. The carotenoid compounds have been widely used as naturaldyes, and recently, these compounds are reported to have excellentanti-tumor effect, by virtue of their selective reactivity with radicalsand singlet oxygen known as carcinogens. In these circumstances, avariety of commercial products containing carotene, including cosmeticsor taste food, have been merchandised. However, there still remainconflict opinions on the anti-tumor activity of beta-carotene, sincebeta-carotene is reported to have a harmful effect on smokers orpatients having lung cancer. Thus, people pay more increasing attentionto lycopene, having stronger anti-oxidation ability with no conflictopinion on the anti-tumor activity.

To meet such a tendency, the requirement of developing a process foreffectively synthesizing polyene chain structures that constructlycopene also increases.

In the meanwhile, the most representative conventional synthetic processfor preparing lycopene was developed by Isler; that is a process forsynthesizing polyene chain on the basis of Wittig reaction (ReactionScheme 1; Helv. Chim. Acta 1956, 39, 463-473).

According to Reaction Scheme 1, C-10 dialdehyde compound is subsequentlyreacted with vinyl ether and propenyl ether compound to form acontinuously conjugated carbon chain wherein each C-2 unit and C-3 unitwas respectively added to the aldehyde groups of C-10 dialdehydecompound. Throughout the stage, C-10 unit has been added to thedialdehyde to form C-20 dialdehyde, of which the triple bond at thecenter of the molecule was then partially reduced to give crocetin.

Then, crocetin thus obtained is subjected to Wittig Reaction with Wittigsalts to form lycopene. The Wittig salts used in this stage is what wasprepared as a result of reaction of geranyl bromide withtriphenylphosphine.

However, the synthetic process for lycopene according to Reaction Scheme1 includes many reaction stages to carry out in order to form crocetin,and the synthetic efficiency is low owing to the trouble in treatingphosphine oxide as the by-product obtained as a result of WittigReaction.

Another synthetic process for synthesizing lycopene is developed byKarrer. The process is based on coupling reaction by using alkynylanion, partial hydrogenation and dehydration. The synthetic process isillustrated in Reaction Scheme 2 (Helv. chim. Acta 1950, 33, 1349-1352).

According to Reaction Scheme 2, an anion obtained by adding metalliczinc to propargylic bromide is subjected to coupling reaction withψ-ionone, to give C-16 intermediate. Then, two molecules of the alkynylanion obtained by adding bases to the C-16 intermediate were coupledwith C-8 diketone compound to form forwards containing 40 carbon atomsrequired for synthesis of lycopene. The partial hydrogenation of the twotriple bonds and dehydration of the forward compound provide lycopene.

The synthetic process for lycopene according to Reaction Scheme 2 isrelatively simple, however, it is not easy to form a double bond havingtrans configuration.

Thus, the first technical object of the present invention is to providean allylic sulfide, that is, a C-5 compound usable for chain extensionto effectively synthesize polyene chain structure described above.

Another technical object of the present invention is to provide aprocess for extending the carbon chain by the use of said allylicsulfide.

Still another object of the present invention is to provide a processfor preparing polyene chain compounds, especially lycopene, by usingsaid process for extending carbon chain.

DISCLOSURE OF THE INVENTION

In order to achieve the first technical object, the present inventionprovides allylic sulfides represented by Chemical Formula 1:

Chemical Formula 1

Wherein, X is selected from the group consisting of —Cl, —Br, —I,—OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph represents phenylgroup.

The second technical object of the present invention is achieved by aprocess for preparing an allylic sulfide of Chemical Formula 1, whichcomprises the steps of (a-1) oxidizing isoprene to obtain isoprenemonoxide, (b-1) reacting the isoprene monoxide with benzene thiol toobtain 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A); and (c-1)reacting the compound (A) with a halogenating compound or sulfonylatingcompound.

In the formulas, X is selected from the group consisting of —Cl, —Br,—I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph representsphenyl group.

The third technical object of the present invention is achieved by aprocess for extending carbon chain by the use of allylic sulfide ofChemical Formula 1, which comprises the steps of (a-2) deprotonatingallylic sulfone compound (B), and reacting the resultant compound withallylic sulfide of Chemical Formula 1 to obtain thio-sulfone compound(C); and (b-2) selectively oxidizing the thio-sulfone compound (C) toobtain the corresponding allylic sulfone compound (D).

In the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂ CH₃, and Ph represents phenyl group.

The fourth technical object of the present invention is achieved by aprocess for preparing a carotenoid polyene chain compound represented byChemical formula 2, which comprises the steps of (a-3) deprotonating theallylic disulfone compound (D), and reacting the resultant compound withnot more than 0.5 equivalent of diallylic sulfide (E) (wherein, Y is ahalogen atom) on the basis of 1 equivalent of allylic disulfone compound(D) to obtain allylic sulfide compound (F); (b-3) selectively oxidizingthe allylic sulfide compound (F) to obtain allylic sulfone compound (G);(c-3) subjecting the allylic sulfone compound (G) to Ramberg-Baklundreaction to give tetra(phenylsulfonyl)-triene compound (H); and (d-3)reacting the compound (H) with a base. If R of Chemical Formula 2 isprenyl, the process provides lycopene.

In the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, Y is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃, and Ph represents phenyl group.

In the process for preparing an allylic sulfide of Chemical Formula 1,the ring opening of isoprene monoxide of stage (b-1) is preferablyperformed by using Cu(I)-containing salt as a catalyst, andN,N-dimethylformamide (DMF) as solvent, because the objective compoundhaving a double bond of trans configuration can be obtained as majorproduct under such reaction conditions.

In the process for extending carbon chain by the use of allylic sulfideof Chemical Formula 1, specific examples of R include methyl, ethyl andpropyl group for C1˜C30 alkyl group, vinyl, allyl and prenyl group forC1˜C30 alkenyl group, and phenyl and naphthyl group for aryl group. X ispreferably Cl or Br in terms of reactivity, while R is preferablyhydrogen or prenyl.

Further, the C-5 unit can be added as desired by repeating stage (a-2)and (b-2) one or more times by using compound (D) as the startingmaterial.

Selective oxidation of stage (b-2) can be preferably performed by addinghydrogen peroxide solution dropwise to thio-sulfone compound (C) in thepresence of a metal oxide catalyst such as lithium molybdenate-niobate(LiNbMoO₆) or vanadium oxide (V₂O₅) at room temperature. Selectiveoxidation under such reaction conditions gives excellent yields.

In the process for preparing a carotenoid polyene chain compoundrepresented by Chemical formula 2, specific examples of R includemethyl, ethyl and propyl group for C1˜C30 alkyl group, vinyl, allyl andprenyl group for C1˜C30 alkenyl group, and phenyl and naphthyl group foraryl group. In particular, it is preferable that R is hydrogen orprenyl.

In the stage (a-3), Y of compound (E) is preferably Br in terms ofreactivity, if R of allylic disulfone compound (D) is hydrogen orprenyl. Deprotonation of allylic disulfone compound (D) should beperformed by adding 2 equivalent of base to 1 equivalent of allylicdisulfone compound (D) at low temperature, preferably at a temperaturenot higher than −40° C. Specific examples of the base include n-BuLi,s-BuLi, t-BuLi, phenyl lithium, NaNH₂, lithium diisopropylamide (LDA),lithium hexamethyldisilazide, sodium hexamethyldisilazide, and the like.

Selective oxidation of stage (b-3) can be preferably performed by addinga mixture of urea-hydrogen peroxide (UHP) and phthalic anhydridedropwise to allylic disulfone compound (D) at low temperature, or addinghydrogen peroxide solution dropwise to sulfide compound (D) in thepresence of a metal oxide catalyst such as lithium molybdenate-niobate(LiNbMoO₆) or vanadium oxide (V₂O₅) at room temperature.

Ramberg-Baklund reaction of stage (c-3) is preferably carried out undera condition excluding oxygen in the air, for example, under nitrogen orargon atmosphere in terms of reactivity and yield.

The base used in stage (d-3) is not particularly restricted. Specificexamples include NaNH₂/NH₃, and metal alkoxides such as CH₃OK/CH₃OH,CH₃ONa/CH₃OH, CH₃CH₂OK/CH₃CH₂OH, CH₃CH₂ONa/CH₃CH₂OH and t-BuOK/t-BuOH.Among them, metal alkoxide is more preferably used as the base.

The allylic sulfide of Chemical Formula 1 according to the presentinvention, which can be used as a ground material for chain extensiondue to the bonding with allylic sulfone compound in the course ofsynthesizing a polyene chain containing compound, is synthesized asdescribed below:

Firstly, isoprene is oxidized to give isoprene monoxide. Though theoxidation reaction may be carried out under a conventional oxidativereaction condition, the present invention employs the condition of usingan oxidant such as m-chloroperoxybenzoic acid (MCPBA), or of forming acorresponding halohydrin from isoprene (J. Am. Chem. Soc., 1950, 72,4608-4613) which is then reacted with a base. Among them, the latter ismore preferable as considering regio-selectivity of the two double bondsof isoprene on the electrophilic reactant.

Then, the isoprene monoxide is reacted with benzene thiol (PhSH) toprovide 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A). In thereaction, it is preferable to employ Cu(I)-containing salt as acatalyst, and N,N-dimethylformamide as solvent in the aspect ofreactivity and yield. Under these reaction conditions, the reactivity ishigh so that the reaction can be performed under mild condition atambient temperature, and the reaction process itself is simple and easyto provide economic and practical advantages. The yield is also good. Asthe Cu(I)-containing salt, any salt having Cu⁺ ion is usable, but CuCN,CuBr, CuI or CuCl is preferably used. The Cu(I)-containing salt is usedin a catalytic amount, more specifically, 0.001˜0.1 mol % of the salt ispreferably used on the basis of 1 mole of isoprene monoxide.

As a result of the above reaction, ring opening at the allylic positionof the epoxide compound is performed. In the4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) molecules thus obtained,trans configuration prevails in a trans:cis ratio of 6:1 or more.

Thereafter, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) is subjectedto halogenation or sulfonylation to provide allylic sulfide of ChemicalFormula 1. In this stage, halogenation of 4-hydroxy-3-methyl-2-butenylphenyl sulfide (A) may be carried out under various reaction conditions.For example, halogenation can be performed by employing a reactioncondition of CH₃SO₂Cl/LiCl, SOCl₂, (COCl)₂, PPh₃/CCl₄, HCl, PBr₃,PPh₃/NBS or HBr. Sulfonylation may be carried out under variousconditions as well, for example under the condition of using a sulfonylcompound such as CF₃SO₂Cl, PhSO₂Cl, CH₃C₆H₄SO₂Cl and CH₃SO₂Cl with abase such as triethylamine (Et₃N) and pyridine (Reaction Scheme 3).

In the formulas, X is selected from the group consisting of —Cl, —Br,—I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, preferably from —Cland —Br.

Now, the reaction of ring opening at the allylic position of theisoprene monoxide is described in detail.

The ring opening reaction of isoprene monoxide may be carried out underthe conditions other than the reaction condition used in the presentinvention. Specific reaction conditions and the product distributionunder each condition are shown in Table 1 below. In Table 1, Entry 5corresponds to the reaction by using Cu(I)-containing salt andbenzenethiol according to the present invention, while Entries 1 to 3 tothe reaction of isoprene monoxide under basic condition, and Entries 4and 6 to the reaction under acidic condition. The ratios of cis:transdouble bond in 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) aredetermined by using gas chromatography and ¹H-NMR.

TABLE 1

Product ratio Yield (A) Entry Reaction Condition (%) (I) (J) (cis:trans)1 Et₃N, PhSH in MeOH, 99 96  3 1 0° C.˜room temperature, 6 Hr 2 NaH,PhSH in THF, 96 98 — 2 0° C.˜room temperature, 6 Hr 3 n-BuLi, PhSH inTHF, 100 100  — — −78° C.˜room temperature, 6 Hr 4 LiClO₄, PhSH in DMF,44 60 18 22(1:4) room temperature, 6 Hr 5 CuI(cat.), PhSH in DMF, 99 —12 87(1:6) room temperature, 6 Hr 6 AlEt₃, PhSH in benzene, 94 —  793(100:0) room temperature, 6 Hr 7 Pd(Ph₃)₄(cat.), 3 — — 100(1:9) PhSHin THF, room temperature, 6 Hr 8 Pd(OAc)₂/PPh₃(cat.), 7 — — 100(1:12)PhSH in THF, room temperature, 6 Hr

As shown in Table 1, in case of Entries 1 to 3, compound (I) wasobtained as the main product, while the desired4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) was not produced at all,or was produced in an extremely small amount. In case of Entry 4,4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) was synthesized at a lowyield of about 22%, and the cis:trans ratio showed relatively low transproduct (1:4) as compared to Entry 5.

In case of Entry 6 (Tetrahedron Lett. 1981, 22, 2413-2416), the desiredcompound, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) could beobtained at a high yield of 93%, however, only to providecis-configuration of compound (A). In case of Entries 7 and 8,4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) of which transconfiguration prevails could be obtained, however, the synthetic yieldof 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) was very low (3% and7%, respectively).

On the contrary, in case of Entry 5, the reaction condition of thepresent invention, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) wasobtained with an excellent yield of about 87%, and the transconfiguration prevails with cis:trans ratio of 1:6 or less. As shownabove, 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A) of which transconfiguration of double bond prevails could be synthesized at a highyield under the reaction condition according to the present invention.

In the meanwhile, in order to synthesize the carotenoid polyene chaincompounds of Chemical Formula 2, which is represented by lycopene, theallylic sulfone compound (D) having extended carbon chain as desiredshould be firstly synthesized. As referring to Reaction Scheme 4, theprocess for preparing di(allylic sulfone) compound (D) is describedhere-in-below:

After deprotonation of the starting material, allylic sulfone compound(B), by treating with base, allylic sulfide of Chemical Formula 1 isadded thereto, to obtain thio-sulfone compound (C) with 5-carbon chainextended. The specific examples of the allylic sulfone compound (B)include geranyl sulfone (R=prenyl) and prenyl sulfone (R=hydrogen). Asthe base, n-butyl lithium (n-BuLi) is preferably used.

The chain extension may be carried out at ambient temperature, but morepreferably at a low temperature of 0° C. or lower. In case of chainextension by using geranyl sulfone as the starting material, X of thecompound of Chemical Formula 1 is preferably Br in terms of reactivity.

Then, the sulfide group of thio-sulfone compound (C) is selectivelyoxidized to provide the corresponding allylic disulfone compound (D).The selective oxidation is preferably carried out under the condition ofemploying metal oxide such as LiNbMoO₆ or V₂O₅ as a catalyst, andhydrogen peroxide (H₂O₂) as an oxidant.

In the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃.

When R is —CN, —COOR′ (wherein, R′ is C₁C10 alkyl group) or —C(═O)H, thecorresponding compound can be prepared according to conventionalprocesses to introduce such a functional group.

If the process for chain extension is repeated, novel allylic sulfonecompounds with increased five carbon numbers can be obtained every time.

Now, the synthesis of carotenoid polyene chain compound represented byChemical Formula 2 according to the present invention is described indetail (see Reaction Scheme 5). The process for preparing carotenoidpolyene chain compound according to the present invention is based onthe process for synthesizing beta-carotene developed by the presentinventors (J. Org. Chem. 1999, 64, 8051-8053). It is characterized byusing di(haloallylic) sulfide (E) in order to synthesize C-10 trienestructure of the center of the polyene chain, and applyingRamberg-Bäklund reaction to diallylic sulfone obtained by oxidation ofthe sulfide compound.

In order to obtain the carbon skeletal required for carotenoids,di(haloallylic) sulfide (E) is combined with 2 equivalents or more ofallylic disulfone compound (D) based on 1 equivalent of compound (E) bymeans of Julia method (Bull. Soc. Chim. Fr., 1973, 743-750), to obtainallylic sulfide (F). The coupling reaction of di(haloallylic) sulfide(E) with allylic disulfone compound (D) is preferably carried out byadding 2 equivalents of base such as n-BuLi to allylic disulfonecompound (D) to deprotonate the compound, and then the reaction isperformed under a temperature condition of −40° C. or lower. Indi(haloallylic) sulfide (E), Y is preferably Br in terms of reactivity.

Then, only the sulfur of allylic sulfide (F) is selectively oxidized togive the corresponding sulfone compound (G). The selective oxidationreaction is preferably carried out by adding a mixture of UHP andphthalic anhydride dropwise to allylic sulfide compound (F) at a lowtemperature, or by adding H₂O₂ dropwise to the compound in the presenceof LiNbMoO₆ or V₂O₅ as a catalyst at ambient temperature. Under such areaction condition, only sulfur is selectively oxidized withoutoxidation of the double bond of allylic sulfide (F).

Thereafter, SO₂ at the center of the structure of sulfone compound (G)is removed to form a double bond to provide compound (H). This reactionis preferably performed by treating sulfone compound (G) underRamberg-Bäklund reaction condition (J. Am. Chem. Soc., 1969, 91,7510-7512).

Lastly, four benzenesulfonyl groups are removed from compound (H) byheating the compound in the presence of alcohol solvent and alkoxidebase such as sodium alkoxide, to synthesize the polyene chain compoundof Chemical Formula 2 represented by lycopene.

In the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃.

When the carotenoid compounds represented by lycopene are preparedaccording to the present invention (Example 1 to 10), the syntheticprocess is simpler, easier and more efficient than conventionalprocesses. In addition, the problem of treating byproducts such asphosphine oxide can be prevented according to the present invention. Theprocess of the present invention is also advantageous in easily formingthe polyene chain structure having trans configuration of double bond.

Allylic sulfide compound of Chemical Formula 1 according to the presentinvention is very useful for an intermediate compound to extend C5chain, during the course of synthesis of polyene chain compound such aslycopene.

According to the present invention, a carotenoid polyene chain compoundrepresented by lycopene of Chemical Formula 2 can be prepared bycoupling of allylic sulfone compound (D) of the desired chain length anddi(haloallylic) sulfide compound (E), and oxidizing the sulfide to givethe corresponding diallylic sulfone compound, which is then subjected toRamberg-Bäklund reaction, and finally eliminating the sulfonyl groups togive conjugated double bonds.

The invention is described in more detail by referring to the examplesbelow, but it should be noticed that the present invention is notrestricted to the examples by any means.

EXAMPLE 1 2-Methyl-4-phenylthio-2-buten-1-ol

Isoprene monoxide (0.30 ml, 3.1 mmol) was dissolved inN,N-dimethylformamide (DMF) (7 ml), and cuprous iodide (CuI) (15 mg,0.08 mmol) and benzene thiol (PhSH) (0.33 ml, 3.2 mmol) were addedthereto at 0° C. The resultant reaction mixture was stirred at the sametemperature for about 6 hours.

When the reaction was completed, the reaction mixture was diluted withether, washed with 1M-HCl three times (10 ml×3), dried over anhydroussodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain2-methyl-4-phenylthio-2-butene-1-ol (0.52 g, 2.7 mmol) (yield: 87%).According to the analytical data of ¹H-NMR and gas chromatography, theratio of trans- to cis-double bond was not less than 6:1.

¹H-NMR: trans δ1.56 (s,3H), 2.38 (br s, 1H),3.55 (d, 2H, J=7.7 Hz), 3.92(s, 2H), 5.54 (t, 1H, J=7.7 Hz), 7.15˜7.35 (m, 5H); cis δ1.75 (s, 3H),2.38 (br s, 1H), 3.52 (d, 2H, J=7.9 Hz), 3.90 (s, 2H), 5.41 (t, 1H,J=7.9 Hz), 7.15˜7.35 (m, 5H). ¹³C-NMR: δ13.6, 31.5, 67.7, 119.9, 126.2,128.9, 129.8, 136.3, 139.0. HRMS(EI) C₁₁H₁₄OS Calculated: 194.0765,Measured: 194.0771.

EXAMPLE 2 4-Bromo-3-methyl-2-butenyl phenyl sulfide

To a solution of 2-methyl-4-phenylthio-2-butene-1-ol (23.7 g, 122 mmol)dissolved in ether (80 ml), PBr₃ (16.5 g, 61 mmol) was slowly added at0° C. The resultant reaction mixture was stirred at 0° C. for about 1hour. When the reaction was completed, the reaction mixture was dilutedwith ether, washed with distilled water, dried over anhydrous sodiumsulfate, and filtered. The filtrate was concentrated by evaporationunder reduced pressure, and the residue was purified by silica gelcolumn chromatography to obtain 4-bromo-3-methyl-2-butenyl sulfide (26.8g, 104 mmol) (yield: 85%)

¹H-NMR: trans δ1.64 (s, 3H), 3.51 (d, 2H, J=7.7 Hz), 3.92 (s, 2H), 5.72(t, 1H, J=7.7 Hz), 7.18˜7.41 (m, 5H); cis 6 1.85 (s, 3H), 3.56 (d, 2H,J=7.9 Hz), 3.79 (s, 2H), 5.52 (t, 1H, J=7.9 Hz), 7.18˜7.41 (m, 5H).¹³C-NMR: δ14.7, 32.4, 40.4, 125.9, 126.7, 128.9, 130.9, 135.4, 135.5.

EXAMPLE 3-1 5-Phenylsulfonyl-1-phenylthio-3,7,11-trimethyl-2,6,10-dodecatriene

Geranyl sulfone (28.7 g, 103 mmol) was dissolved in THF (150 ml), andn-BuLi (1.6M solution in hexane/64 ml, 103 mmol) was slowly addedthereto at 0° C. The resultant mixture was stirred for 20 minutes, and4-bromo-3-methyl-2-butenyl phenyl sulfide (29.1 g, 113 mmol) was addedto the reaction mixture. The reaction temperature was slowly raised toroom temperature, and the mixture was stirred at the same temperaturefor about 11 hours.

To the reaction mixture, ether 100 ml was added, and the resultantmixture was subsequently washed with aqueous 1M-HCl solution (20 ml×2)and distilled water (30 ml). The mixture was dried over anhydrous sodiumsulfate, and filtered.

The filtrate was concentrated by evaporation under reduced pressure, andthe residue was purified by silica gel column chromatography to obtain5-phenylsulfonyl-1-phenylthio-3,7,11-trimethyl-2,6,10-dodecatriene (43.6g, 96 mmol) (yield: 93%).

¹H-NMR: δ1.13 (s, 3H), 1.53 (s, 3H), 1.59 (s, 3H), 1.68 (s, 3H), 1.92(br s, 4H), 2.31 (dd, 1H, J=13.2, 11.4 Hz), 2.90 (dd, 1H, J=13.2, 3.0Hz), 3.48 (d, 2H, J=7.5 Hz), 3.87 (ddd, 1H, J=11.4, 10.3, 3.0 Hz), 4.88(d, 1H, J=10.3 Hz), 5.01 (br s, 1H), 5.32 (t, 1H, J=7.5 Hz), 7.15˜7.38(m, 5H), 7.40˜7.58 (m, 2H), 7.58˜7.70 (m, 1H), 7.75˜7.90 (m, 2H).¹³C-NMR: δ16.0, 16.4, 17.7, 25.7, 26.2, 31.8, 37.1, 39.6, 63.2, 116.8,123.0, 123.6, 126.1, 128.7, 128.8, 129.3, 129.5, 131.9, 133.5, 134.6,136.5, 137.6, 145.6.

EXAMPLE 3-2 5-Phenylsulfonyl-1-phenylthio-3,7-dimethyl -2,6-octadiene

Prenyl sulfone (20.2 g, 103 mmol) was dissolved in THE (100 ml), andn-BuLi (1.6M solution in hexane/72 ml, 115 mmol) was slowly addedthereto at 0° C. The resultant mixture was stirred for 20 minutes, and4-bromo-3-methyl-2-butenyl phenyl sulfide (25.9 g, 101 mmol) was addedto the reaction mixture. The reaction temperature was slowly raised toroom temperature, and the mixture was stirred at the same temperaturefor about 3 hours.

To the reaction mixture, ether 100 ml was added, and the resultantmixture was subsequently washed with aqueous 1M-HCl solution (20 ml×2)and distilled water (30 ml). The mixture was dried over anhydrous sodiumsulfate, and filtered.

The filtrate was concentrated by evaporation under reduced pressure, andthe residue was purified by silica gel column chromatography to obtain5-phenylsulfonyl-1-phenylthio-3,7-dimethyl-2,6-octadiene (33.9 g, 87.7mmol) (yield: 91%).

¹H-NMR: δ1.11 (s, 3H), 1.52(s, 3H), 1.61 (s, 3H), 2.31 (dd, 1H,J=13.6,11.6 Hz), 2.86 (dd, 1H, J=13.6, 2.9 Hz), 3.48 (d, 2H, J=7.7 Hz), 3.84(ddd, 1H, J=11.6, 10.4, 2.9 Hz), 4.86 (ddd, 1H, J=10.3, 1.4, 1.3 Hz),5.31 (t, 1H, J=7.7 Hz), 7.15˜7.30 (m, 5H), 7.48˜7.53 (m, 2H), 7.59˜7.61(m, 1H), 7.80˜7.82 (m, 2H). ¹³C-NMR: δ16.0, 17.9, 25.7, 31.8, 37.0,63.3, 117.0, 123.1, 126.1, 128.7, 128.7, 129.2, 129.6, 133.4, 134.5,136.4, 137.7, 145.1.

EXAMPLE 4-1 1,5-Di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene

In methyl alcohol (20 ml), dissolved was5-phenylsulfonyl-1-phenylthio-3,7,11-trimethyl-2,6,10-dodecatriene (1.00g, 2.2 mmol), and LiNbMoO₆ (32 mg, 0.11 mmol) and H₂O₂ (30% aqueoussolution) (0.75 g, 6.6 mmol) were added thereto. The resultant reactionmixture was stirred at room temperature for about 5 hours.

When the reaction was completed, the reaction mixture was concentratedby evaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain1,5-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene (804 mg, 1.7mmol) (yield: 75%).

¹H-NMR: δ1.15 (s, 3H), 1.36 (s, 3H), 1.58 (s, 3H), 1.67 (s, 3H), 1.94(br s, 4H), 2.33 (dd, 1H, J=13.7, 11.4 Hz), 2.93 (d, 1H, J=13.7 Hz),3.75 (d, 2H, J=8.0 Hz), 3.86 (dt, 1H, J_(d)=2.6, J_(t)=10.4 Hz), 4.87(d, 1H, J=10.4 Hz), 5.00 (s, 1H), 5.18 (t, 1H, J=8.0 Hz), 7.48˜7.58 (m,4H), 7.60˜7.69 (m, 2H), 7.78˜7.88 (m, 4H). ¹³C-NMR: δ16.3, 16.3,17.7,25.7,26.1,37.2, 39.7, 55.9, 63.0, 113.6, 116.6, 123.5, 128.3,128.8, 129.1, 129.3, 132.0, 133.6, 133.7, 137.5, 138.8, 141.5, 146.1.

EXAMPLE 4-2 1,5-Di(phenylsulfonyl)-3,7-dimethyl-2,6-octadiene

In methyl alcohol (80 ml), dissolved was5-phenylsulfonyl-1-phenylthio-3,7-dimethyl-2,6-octadiene (8.62 g, 22.3mmol), and LiNbMoO₆ (330 mg, 1.12 mmol) and H₂O₂ (30% aqueous solution)(7.58 g, 66.9 mmol) were added thereto. The resultant reaction mixturewas stirred at room temperature for about 11 hours.

When the reaction was completed, the reaction mixture was concentratedby evaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain1,5-di(phenylsulfonyl)-3,7-dimethyl-2,6-octadiene (8.84 g, 21.1 mmol)(yield: 95%).

¹H-NMR: δ1.11 (s, 3H), 1.35 (s, 3H), 1.66 (s, 3H), 2.34 (dd, 1H, J=13.8,11.5 Hz), 2.89 (dd, 1H, J=13.8, 2.9 Hz), 3.77 (d, 2H, J=7.9 Hz), 3.85(ddd, 1H, J=11.5, 10.4, 2.9 Hz), 4.86 (d, 1H, J=10.4 Hz), 5.16 (t, 1H,J=7.9 Hz), 7.51˜7.56 (m, 4H), 7.62˜7.67 (m, 2H), 7.80˜7.84 (m, 4H).

¹³C-NMR: δ16.2, 17.8, 25.8, 37.0, 55.8, 63.0, 113.5, 116.6, 128.2,128.8, 129.1, 129.1, 133.6, 133.7, 137.3, 138.7, 141.3, 142.7.

EXAMPLE 55,9-Di(phenylsulfonyl)-1-phenylthio-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene

1,5-Di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene (6.20 g,12.7 mmol) was dissolved in THF (25 ml), and n-BuLi (1.6M solution inhexane/19 ml, 30.5 mmol) was slowly added thereto at −78° C. Theresultant mixture was stirred for 30 minutes, and4-bromo-3-methyl-2-butenyl phenyl sulfide (3.6 g, 14.0 mmol) was addedto the reaction mixture. The reaction mixture was stirred at −78° C. forabout 3 hours and quenched with 1M-HCl solution (20 ml).

The mixture was slowly warmed up to room temperature and extracted withether (100 ml). The ether extract was subsequently washed with distilledwater (30 ml), dried over anhydrous sodium sulfate, and filtered.

The filtrate was concentrated by evaporation under reduced pressure, andthe residue was purified by silica gel column chromatography to obtain5,9-di(phenylsulfonyl)-1-phenylthio-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene(7.66 g, 11.6 mmol) (yield: 91%).

¹H-NMR: δ1.16 (d, 3H, J=1.1 Hz), 1.35 (s, 3H), 1.47 (s, 3H), 1.58 (s,3H), 1.67 (s, 3H), 1.94 (br s, 4H), 2.14 (dd, 1H, J=13.2, 11.9 Hz), 2.26(dd, 1H, J=13.6, 11.5 Hz), 2.73 (d, 1H, J=13.0 Hz), 2.91 (d, 1H, J=12.8Hz), 3.44 (d, 2H, J=7.8 Hz), 3.72˜3.94 (m, 2H), 4.85 (d, 1H, J 9.3 Hz),4.92 (d, 1H, J=9.6 Hz), 5.02 (br s, 1H), 5.24 (t, 1H, J=7.8 Hz),7.14˜7.33 (m, 5H), 7.40˜7.55 (m, 4H), 7.55˜7.67 (m, 2H), 7.70˜7.87 (m,4H).

¹³C-NMR: δ15.9, 16.5, 17.0, 17.7, 25.7, 26.1, 31.7, 37.3, 38.1, 39.9,62.9, 63.4, 117.0, 119.7, 123.2, 123.6, 126.2, 128.7, 128.8, 128.9,129.0, 129.3, 129.5, 131.9, 133.5, 133.7, 134.2, 136.3, 137.4, 137.5,141.2, 145.9.

EXAMPLE 61,5,9-Tri(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene

In methyl alcohol (50 ml), dissolved was5,9-di(phenylsulfonyl)-1-phenylthio-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetrane(7.03 g, 10.6 mmol), and LiNbMoO₆ (77 mg, 0.27 mmol) and H₂O₂ (30%aqueous solution) (3.61 g, 31.8 mmol) were added thereto. The resultantreaction mixture was stirred at room temperature for about 5 hours.

When the reaction was completed, the reaction mixture was diluted withCHCl₃ (100 ml), washed with distilled water (30 ml), dried overanhydrous sodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain1,5,9-tri(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraene(5.33 g, 7.7 mmol) (yield: 72%).

¹H-NMR: δ1.14 (d, 3H, J=1.2 Hz), 1.32 (s, 3H), 1.34 (d, 3H, J=1.1 Hz),1.58 (s, 3H), 1.67 (s, 3H), 1.92 (br s, 4H), 2.15˜2.36 (m, 2H),2.70˜2.98 (m, 2H), 3.72 (d, 2H, J=7.8 Hz), 3.83 (ddd, 1H, J=10.9, 10.9,3.2 Hz), 3.91 (ddd, 1H, J=10.3, 10.3, 3.3 Hz), 4.89 (d, 1H, J=10.3 Hz),4.93 (d, 1H, J=10.9 Hz), 5.02 (br s, 1H), 5.12 (t, 1H, J=7.8 Hz),7.40˜7.71 (m, 9H), 7.71˜7.93 (m, 6H). ¹³C-NMR: δ16.1, 16.4, 16.7, 17.6,25.6, 26.0, 37.6, 38.1, 39.8, 55.7, 62.6, 63.0, 113.7, 117.1, 119.4,123.6, 128.1, 128.7, 128.9, 128.9. 129.1, 129.2, 131.8, 133.5, 133.7,133.7, 137.3, 137.4, 138.8, 140.9, 141.7, 145.8.

EXAMPLE 7-1Di(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfide

In THF (50 ml), dissolved was1,5-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatriene (9.00 g,18.5 mmol). To the solution, n-BuLi (1.6M solution in hexane/23 ml, 37mmol) was slowly added thereto at −78° C. The resultant mixture wasstirred for 20 minutes, and di(4-bromo-3-methyl-2-butenyl sulfide (E)(3.03 g, 9.2 mmol) was added to the reaction mixture. After stirring themixture at the same temperature for 3 hours, aqueous 1M-HCl solution (10ml) was added thereto to quench the reaction.

The temperature of the reaction mixture was slowly raised to roomtemperature, and ether (100 ml) was added. The resultant mixture wassubsequently washed with aqueous 1M-HCl solution (20 ml×2) and distilledwater (30 ml). The mixture was dried over anhydrous sodium sulfate, andfiltered.

The filtrate was concentrated by evaporation under reduced pressure, andthe residue was purified by silica gel column chromatography to obtaindi(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfide (9.39 g, 8.2 mmol) (yield: 89%).

¹H-NMR: δ1.16 (s, 6H), 1.41 (s, 6H), 1.49 (s, 6H), 1.58 (s, 6H), 1.68(s, 6H), 1.95 (br s, 8H), 2.15 (dd, 2H, J=13.0, 11.9 Hz), 2.30 (dd, 2H,J=12.6, 11.0 Hz), 2.73 (d, 2H, J=13.0 Hz), 2.86 (d, 2H, J=12.6 Hz), 2.95(d, 4H, J=7.0 Hz), 3.86 (m, 4H), 4.87 (d, 2H, J=10.6 Hz), 4.93 (d, 2H,J=9.9 Hz), 5.02 (br s, 2H), 5.18 (t, 2H, J 7.0 Hz), 7.46˜7.58 (m, 8H),7.58˜7.69 (m, 4H), 7.72˜7.90 (m, 8H). ¹³C-NMR: δ15.8, 16.4, 16.8, 17.6,25.6, 26.0, 28.6, 37.3, 38.4, 39.8, 62.9, 63.2, 116.8, 119.8, 123.5,124.3, 128.7, 128.8, 129.0, 129.2, 131.9, 133.2, 133.5, 133.6, 137.4,137.5, 141.1, 146.0.

EXAMPLE 7-2Di(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfide

In THF (50 ml), dissolved was1,5-di(phenylsulfonyl)-3,7-dimethyl-2,6-octadiene (4.61 g, 11.0 mmol).To the solution, n-BuLi (1.6M solution in hexane/16.5 ml, 26.4 mmol) wasslowly added thereto at −78° C. The resultant mixture was stirred for 20minutes, and di(4-bromo-3-methyl-2-butenyl) sulfide (E) (1.75 g, 5.33mmol) was added to the reaction mixture. After stirring the mixture atthe same temperature for 3 hours, aqueous 1M-HCl solution (10 ml) wasadded thereto to quench the reaction.

The temperature of the reaction mixture was slowly raised to roomtemperature, and ether (100 ml) was added. The resultant mixture wassubsequently washed with aqueous 1M-HCl solution (20 ml×2) and distilledwater (30 ml). The mixture was dried over anhydrous sodium sulfate, andfiltered.

The filtrate was concentrated by evaporation under reduced pressure, andthe residue was purified by silica gel column chromatography to obtaindi(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfide(4.80 g, 4.79 mmol) (yield: 87%).

¹H-NMR: δ1.12 (s, 6H), 1.42 (s, 6H), 1.49 (s, 6H), 1.69 (s, 6H),2.03˜2.38 (m, 4H), 2.65˜3.20 (m, 8H), 3.88 (m, 4H), 4.82 (d, 2H, J=10.2Hz), 4.91 (d, 2H, J=9.9 Hz), 5.12 (t, 2H, J=7.3 Hz), 7.53˜7.65 (m, 12H),7.76˜7.84 (m, 8H). ¹³C-NMR: δ15.8, 16.8, 17.9, 25.9, 28.5, 37.1, 38.4,62.8, 63.1, 116.9, 119.6, 124.4, 128.8, 128.8, 128.9, 129.1, 133.7,136.7, 137.1, 137.2, 140.4, 140.9, 142.7.

EXAMPLE 8-1Di(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfone

In methyl alcohol (20 ml), dissolved wasdi(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenylsulfide (2.0 g, 1.75 mmol), and LiNbMoO₆ (26 mg, 0.09 mmol) and H₂O₂(30% aqueous solution) (0.99 g, 8.75 mmol) were added thereto. Theresultant reaction mixture was stirred at room temperature for about 5hours.

When the reaction was completed, the reaction mixture was concentratedby evaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtainDi(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfone (1.48 g, 1.26 mmol) (yield: 72%).

¹H-NMR: δ1.15 (s, 6H), 1.41 (s, 6H), 1.58 (s, 6H), 1.61 (s, 6H), 1.67(s, 6H), 1.93 (br s, 8H), 2.17˜2.37 (m, 4H), 2.81 (d, 2H, J=12.3 Hz),2.91 (d, 2H, J=14.1 Hz), 3.56 (d, 4H, J=7.2 Hz), 3.91 (dt, 4H,J_(d)=2.8, J_(t)=9.6 4.89 (d, 2H, J=8.8 Hz), 4.92 (d, 2H, J=10.1 Hz),5.01 (br s, 2H), 5.23 (t, 2H J=7.2 Hz), 7.47˜7.58 (m, 8H), 7.58˜7.67 (m,4H), 7.74˜7.89 (m, 8H). ¹³C-NMR: δ16.4, 16.5, 16.6, 17.6, 25.6, 26.0,37.7, 38.4, 39.7, 51.6, 62.5, 62.8, 113.7, 116.9, 118.5, 123.6, 128.7,128.9, 128.9, 129.2, 131.7, 133.5, 133.7, 137.2, 140.8, 140.9, 141.6,145.8.

EXAMPLE 8-2Di(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfone

In methyl alcohol (50 ml), dissolved wasdi(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfide(4.54 g, 4.52 mmol), and LiNbMoO₆ (66 mg, 0.23 mmol) and H₂O₂ (30%aqueous solution) (1.54 g, 13.6 mmol) were added thereto. The resultantreaction mixture was stirred at room temperature for about 6 hours.

When the reaction was completed, the reaction mixture was concentratedby evaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtainDi(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfone(3.28 g, 3.16 mmol) (yield: 70%).

¹H-NMR: δ1.05 (s, 6H), 1.41 (s, 6H), 1.61 (s, 6H), 1.67 (s, 6H),2.17˜2.47 (m, 4H), 2.74˜2.99 (m, 4H), 3.57 (br s, 4H), 3.79˜4.02 (m,4H), 4.86 (d, 2H, J=9.9 Hz), 4.90 (d, 2H, J=10.8 Hz), 5.21 (t, 2H, J=7.5Hz), 7.51˜7.55 (m, 8H), 7.61˜7.66 (m, 4H), 7.76˜7.82 (m, 8H). ¹³C-NMR:δ16.6, 16.7, 17.9, 25.9, 37.5, 38.7, 51.6, 62.6, 62.8, 113.7, 117.1,119.4, 128.8, 129.0, 129.0, 129.2, 133.6, 133.8, 137.1, 141.0, 141.0,141.6, 142.7.

EXAMPLE 9-1 7,7′,11,11′-Tetra(phenylsulfonyl)-7,7′,8,8′,11,11′,12,12′-octahydrolycopene

Di(5,9-di(phenylsulfonyl)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)sulfone(1.10 g, 0.94 mmol) was dissolved in a mixture of t-butanol (30 ml) andCCl₄ (30 ml). Minutely pulverized KOH (1.68 g, 30.0 mmol) was addedthereto under argon atmosphere at room temperature. The reaction mixturewas vigorously stirred for 5 hours.

When the reaction was completed, methylene chloride (60 ml) was addedthereto to dissolve the mixture, and the resultant solution was washedwith 1M-HCl (20 ml). The combined methylene chloride layer was driedover anhydrous sodium sulfate, and filtered. The filtrate wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain7,7′,11,11′-tetra(phenylsulfonyl)-7,7′,8,8′,11,11′,12,12′-octahydrolycopene(822 mg, 0.74 mmol) (yield: 79%).

¹H-NMR: δ1.14 (br s, 6H), 1.33 (s, 6H), 1.58 (s, 6H), 1.60 (s, 6H), 1.67(s, 6H), 1.93 (br s, 8H), 2.16˜2.42 (m, 4H), 2.63˜3.07 (m, 4H),3.68˜4.05 (m, 4H), 4.91 (d, 4H, J=10.6 Hz), 4.98 (br s, 2H), 5.69˜5.90(br s, 2H), 6.08˜6.24 (m, 2H), 7.45˜7.58 (m, 8H), 7.58˜7.70 (m, 4H),7.73˜7.87 (m, 8H). ¹³C-NMR: δ16.4, 17.1, 17.7, 24.9, 25.6, 26.1, 28.5,37.9, 39.8, 63.0, 63.6, 116.6, 116.8, 119.9, 123.5, 127.8, 128.7, 128.8,129.0, 129.1, 129.2, 132.0, 133.6, 137.5, 140.6, 141.4, 145.9, 146.1.

EXAMPLE 9-22,6,10,15,19,23-Hexamethyl-4,8,17,21-tetra(phenylsulfonyl)-2,6,10,12,14,18,22-tetraeicosaheptaene

Di(5,9-di(phenylsulfonyl)-3,7,11-trimethyl-2,6,10-dodecatrienyl) sulfone(1.17 g, 1.13 mmol) was dissolved in a mixture of t-butanol (30 ml) andCCl₄ (30 ml). Minutely pulverized potassium hydroxide (KOH/1.90 g, 33.8mmol) was added thereto under argon atmosphere at room temperature. Thereaction mixture was vigorously stirred for 7 hours.

When the reaction was completed, methylene chloride (70 ml) was addedthereto to dissolve the mixture, and the resultant solution was washedwith 1M-HCl (20 ml). The combined methylene chloride layer was driedover anhydrous sodium sulfate, and filtered. The filtrate wasconcentrated by evaporation under reduced pressure, and the residue waspurified by silica gel column chromatography to obtain2,6,10,15,19,23-hexamethyl-4,8,17,21-tetra(phenylsulfonyl)-2,6,10,12,14,18,22-tetraeicosaheptaene(839 mg, 0.87 mmol) (yield: 77%).

¹H-NMR: δ1.06 (s, 6H), 1.57 (br s, 6H), 1.61 (s, 6H), 1.66 (s, 6H),2.12˜2.52 (m, 4H), 2.68˜3.07 (m, 4H), 3.64˜4.04 (m, 4H), 4.65˜5.03 (m,4H), 5.69˜5.91 (br d, 2H, J=18.5 Hz), 6.08˜6.26 (m, 2H), 7.43˜7.59 (m,8H), 7.59˜7.70 (m, 4H), 7.73˜7.87 (m, 8H).

EXAMPLE 10-1 Lycopene

In a mixture of ethanol (20 ml) and benzene (5 ml), dissolved was7,7′,11,11′-tetra(phenylsulfonyl)-7,7′,8,8′,11,11′,12,12′-octahydrolycopene(H-1) (682 mg, 0.62 mmol). Sodium ethoxide (NaOEt) (3.35 g, 49.3 mmol)was added thereto under argon atmosphere.

The reaction mixture was heated under reflux with vigorous stirring for12 hours.

When the reaction was completed, benzene (50 ml) was added thereto todissolve the mixture, and the resultant solution was washed with 1M-HCl(10 ml). The combined organic layer was dried over anhydrous sodiumsulfate, and filtered. The filtrate was concentrated by evaporationunder reduced pressure, and the residue was purified by silica gelcolumn chromatography to obtain lycopene of Chemical Formula 2 (260 mg,0.48 mmol) (yield: 78%).

¹H-NMR: δ1.61 (s, 6H), 1.68 (s, 6H), 1.82 (s, 6H), 1.96 (s, 12H), 2.11(br s, 8H), 5.11 (br s, 2H), 5.95 (d, 2H, J=10.8 Hz), 6.18 (d, 2H,J=12.1 Hz), 6.24 (d, 2H, J=14.9 Hz), 6.20˜6.30 (m, 2H), 6.35 (d, 2H,J=14.8 Hz), 6.49 (dd, 2H, J=14.9, 10.8 Hz), 6.63 (dd, 2H, J=14.8, 12.1Hz), 6.55˜6.70 (m, 2H). ¹³C-NMR: δ12.8, 12.9, 17.0, 17.7, 25.7, 26.7,40.2, 123.9, 124.8, 125.1, 125.7, 130.1, 131.5, 131.8, 132.6, 135.4,136.2, 136.5, 137.3, 139.5.

The analytical data of lycopene as above corresponds to NMR data oftrans-lycopene as previously reported (Helv. Chim. Acta 1992, 75,1848-1865).

EXAMPLE 10-22,6,10,15,19,23-Hexamethyl-2,4,6,8,10,12,14,16,18,20,22-tetraeicosaundecaene

In a mixture of ethanol (30 ml) and benzene (5 ml), dissolved was2,6,10,15,19,23-hexamethyl-4,8,17,21-tetra(phenylsulfonyl)-2,6,10,12,14,18,22-tetraeicosaheptaene(730 mg, 0.75 mmol). Sodium ethoxide (NaOEt) (4.10 g, 60 3 mmol) wasadded thereto under argon atmosphere.

The reaction mixture was heated under reflux with vigorous stirring for12 hours. Then the reaction was completed, benzene (60 ml) was addedthereto to dissolve the mixture, and the resultant solution was washedwith 1M-HCl (10 ml). The combined organic layer was dried over anhydroussodium sulfate, and filtered. The filtrate was concentrated byevaporation under reduced pressure, and the residue was purified bysilica gel column chromatography to obtain2,6,10,15,19,23-hexamethyl-2,4,6,8,10,12,14,16,18,20,22-tetraeicosaundecaene(213 mg, 0.53 mmol) (yield: 71%).

¹H-NMR: δ1.82 (s, 12H), 1.97 (s, 12H), 5.94 (d, 2H, J=11 Hz), 6.18 (d,2H,J=12.7 Hz), 6.22 (d, 2H, J=15.3 Hz), 6.16˜6.31 (m, 2H), 6.35 (d, 2H,J=14.8 Hz), 6.48 (dd, 2H, J=15.3, 11 Hz), 6.63 (dd, 2H, J=14.8, 12.7Hz), 6.54˜6.67 (m, 2H).

What is claimed is:
 1. An allylic sulfide represented by followingChemical Formula 1: Chemical formula 1

 wherein, X is selected from the group consisting of —Cl, —Br, —I,—OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph represents phenylgroup.
 2. A process for preparing an allylic sulfide of Chemical Formula1, which comprises the steps of (a-1) oxidizing isoprene to obtainisoprene monoxide; (b-1) reacting the isoprene monoxide withbenzenethiol to obtain 4-hydroxy-3-methyl-2-butenyl phenyl sulfide (A);and (c-1) reacting the compound (A) with a halogenating compound orsulfonylating compound.

in the formulas, X is selected from the group consisting of —Cl, —Br,—I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and —OSO₂CH₃, and Ph representsphenyl group.
 3. A process according to claim 2, Cu(I)-containing saltis used as the catalyst and N,N-dimethylformamide (DMF) as the solventin stage (b-1).
 4. A process according to claim 3, wherein theCu(I)-containing salt is one or more salt(s) selected from the groupconsisting of CuCN, CuI, CuBr and CuCl.
 5. A process for extendingcarbon chain by the use of allylic sulfide of Chemical Formula 1, whichcomprises the steps of (a-2) deprotonating allylic sulfone compound (B),and reacting the resultant compound with allylic sulfide of ChemicalFormula 1 to obtain thio-sulfone compound (C); and (b-2) selectivelyoxidizing the thio-sulfone compound (C) to obtain the correspondingallylic sulfone compound (D).

in the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, X is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃, and Ph represents phenyl group.
 6. A process according toclaim 5, wherein C-5 unit is added by repeating stages (a-2) and (b-2)one or more times by using compound (D) as the starting material.
 7. Aprocess according to claim 5, wherein stage (b-2) is performed by addinghydrogen peroxide solution dropwise to the sulfide compound (C) in thepresence of lithium molybdenate-niobate (LiNbMoO₆) or vanadium oxide(V₂O₅) as a catalyst.
 8. A process for preparing a carotenoid polyenechain compound represented by Chemical formula 2, which comprises thesteps of (a-3) deprotonating the allylic disulfone compound (D), andreacting the resultant compound with not more than 0.5 equivalent ofdiallylic sulfide (E) (wherein, Y is a halogen atom) on the basis of 1equivalent of allylic disulfone compound (D) to obtain allylic sulfidecompound (F); (b-3) selectively oxidizing the allylic sulfide compound(F) to obtain allylic sulfone compound (G); (c-3) subjecting the allylicsulfone compound (G) to Ramberg-Bäklund reaction to givetetra(phenylsulfonyl)-triene compound (H); and (d-3) reacting thecompound (H) with a base.

in the formulas, R is selected from the group consisting of hydrogen,C1˜C30 alkyl group, C1˜C30 alkenyl group, aryl group, —CN, —COOR′(wherein, R′ is C1˜C10 alkyl group) and —C(═O)H, Y is selected from thegroup consisting of —Cl, —Br, —I, —OSO₂CF₃, —OSO₂Ph, —OSO₂C₆H₄CH₃ and—OSO₂CH₃, and Ph represents phenyl group.
 9. A process according toclaim 8, wherein R represents hydrogen or prenyl.
 10. A processaccording to claim 8, wherein the deprotonation step of disulfonecompound (D) in stage (a-3) is performed by adding not less than 2equivalent of base dropwise to 1 equivalent of allylic disulfonecompound (D) at a temperature of −40° C. or lower.
 11. A processaccording to claim 8, wherein stage (b-3) is performed by adding amixture of urea-hydrogen peroxide (UHP) and phthalic anhydride toallylic sulfide compound (F) at a low temperature, or by adding hydrogenperoxide (H₂O₂) solution in the presence of LiNbMoO₆ or V₂O₅ as acatalyst at ambient temperature.
 12. A process according to claim 8,wherein Ramberg-Baklund reaction of stage (c-3) is carried out undernitrogen or argon atmosphere.
 13. A process according to claim 8,wherein the base used at stage (d-3) is a metal alkoxide.
 14. A processaccording to claim 9, wherein the deprotonation step of disulfonecompound (D) in stage (a-3) is performed by adding not less than 2equivalent of base dropwise to 1 equivalent of allylic disulfonecompound (D) at a temperature of −40° C. or lower.
 15. A processaccording to claim 9, wherein stage (b-3) is performed by adding amixture of urea-hydrogen peroxide (UHP) and phthalic anhydride toallylic sulfide compound (F) at a low temperature, or by adding hydrogenperoxide (H₂O₂) solution in the presence of LiNbMoO₆ or V₂O₅ as acatalyst at ambient temperature.
 16. A process according to claim 9,wherein Ramberg-Baklund reaction of stage (c-3) is carried out undernitrogen or argon atmosphere.
 17. A process according to claim 9,wherein the base used at stage (d-3) is a metal alkoxide.
 18. An allylicsulfone represented by the following compound (D):

wherein R is selected from the group consisting of hydrogen, C₁-C₆ alkylgroup, C₁-C₆ alkenyl group, and aryl group, and Ph represents phenylgroup.